Rydlo Tali, Rotem Shahar, Mor Amram
Department of Biotechnology & Food Engineering, Technion-Israel Institute of Technology, 32000 Haifa, Israel.
Antimicrob Agents Chemother. 2006 Feb;50(2):490-7. doi: 10.1128/AAC.50.2.490-497.2006.
Antibacterial properties of the frog-derived peptide dermaseptin S4 and a series of synthetic derivatives against the food pathogen Escherichia coli O157:H7 were investigated under extreme incubation conditions. The 28-mer analog K4K20S4 (P28) displayed an MIC of 8 microM and rapid bactericidal kinetics under standard culture conditions. Potent bactericidal properties were maintained at high salt concentrations, under acidic or basic conditions, and at extreme temperatures. The N-terminal 14-mer sequence (P14) displayed higher potency (MIC, 4 microM) but only within a narrow range of incubation conditions, pointing to the importance of the C-terminal domain of P28. The potency range was reextended upon conjugation of aminododecanoic acid to P14. The resulting lipopeptide was even more potent (MIC, 2 microM) and affected bacterial viability under most of the conditions tested, including in commercial apple juice. The mechanistic implications of peptides' hydrophobicity, charge, structure, and binding to an idealized membrane were probed and are discussed here. Collectively, the data indicate interest in simple peptide-based compounds for design of antimicrobials that affect pathogens under a variable range of incubation conditions.
在极端培养条件下，研究了源自青蛙的肽皮防御素S4及其一系列合成衍生物对食源性病原体大肠杆菌O157:H7的抗菌特性。28聚体类似物K4K20S4（P28）在标准培养条件下的最低抑菌浓度（MIC）为8微摩尔，且具有快速杀菌动力学。在高盐浓度、酸性或碱性条件以及极端温度下，其强效杀菌特性得以保持。N端14聚体序列（P14）显示出更高的效力（MIC，4微摩尔），但仅在狭窄的培养条件范围内如此，这表明P28的C端结构域很重要。将氨基十二烷酸与P14偶联后，效力范围得以重新扩展。所得脂肽效力更强（MIC，2微摩尔），并且在大多数测试条件下，包括在市售苹果汁中，均能影响细菌活力。本文探究并讨论了肽的疏水性、电荷、结构以及与理想化膜结合的机制意义。总体而言，这些数据表明基于简单肽的化合物在设计能在可变培养条件下影响病原体的抗菌剂方面具有吸引力。
